Hepatitis B antiviral agents

Patent metadata

Field	Value
Publication number	US-10723733-B2
Application number	US-201816210492-A
Country	US
Kind code	B2
Filing date	Dec 5, 2018
Priority date	Dec 6, 2017
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof:

which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

First claim

What is claimed is:

1. A compound represented by Formula (IIIa-8), or a pharmaceutically acceptable salt thereof,

wherein R 5 is selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, optionally substituted heteroaryl, —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , —S(O) 2 R 11 , —S(O) 2 NR 11 R 12 , and —C(O)NR 12 S(O) 2 R 12 ;
R 11 and R 12 are independently selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl and optionally substituted heteroaryl; and
R 20 is difluoromethyl, cyclopropyl, isopropyl, trifluoromethyl or 2,2,2-trifluoroethyl.

2. A compound represented by Formula (Vb), or a pharmaceutically acceptable salt thereof,

wherein:
X 2 at each occurrence is independently selected from hydrogen or halogen;
W is selected from the group consisting of hydrogen, halogen, —CN, —N 3 , —OR 11 , —CR 11 R 12 R 3 , —NR 11 R 12 , protected hydroxy, protected amino, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, optionally substituted heteroaryl, —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , —NR 11 CONR 11 R 12 , —S(O) 2 R 11 , —S(O) 2 NR 11 R 12 , —NR 11 S(O) 2 R 12 , —NR 11 S(O) 2 NR 11 R 12 , —P(O)(OR 11 ) 2 , and —NR 11 P(O)(OR 11 ) 2 ;
R 3 is selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, —CN, —OR 11 , and —NR 11 R 12 ; R 4 is selected from the group consisting of —NR 11 R 12 , OR 11 , optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl and optionally substituted heteroaryl;
R 15 is hydrogen, halo, CN, —NR 11 R 12 , —N 3 , optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl and optionally substituted heteroaryl; and
R 11 and R 12 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted —C 1 -C 8 alkyl, optionally substituted —C 2 -C 8 alkenyl, optionally substituted —C 2 -C 8 alkynyl, optionally substituted —C 3 -C 8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl and optionally substituted heteroaryl.

3. A compound selected from the compounds set forth below or a pharmaceutically acceptable salt thereof:

Com-

pound
Structure

1

2

5

6

7

8

9

10

11

12

13

14

15

16

Assignees

• Enanta Pharm Inc

Inventors

• Qiu Yao-Ling
• Peng Xiaowen
• Kass Jorden
• Gao Xuri
• Li Wei
• Cao Hui
• Suh Byung-Chul
• Or Yat Sun

Classifications

• A61P31/14

  for RNA viruses · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title